2-(naphthalen-2-yloxy)-1-[(1,1'-biphenyl-4-yl)]ethan-1-one

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-(naphthalen-2-yloxy)-1-[(1,1'-biphenyl-4-yl)]ethan-1-one
• 英文别名: 1-(biphenyl-4-yl)-2-(naphthalen-2-yloxy)ethanone；2-Naphthalen-2-yloxy-1-(4-phenylphenyl)ethanone；2-naphthalen-2-yloxy-1-(4-phenylphenyl)ethanone
• 化学式: C₂₄H₁₈O₂
• 分子量: 338.406
• InChiKey: VJLXPVGIIIYABA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(naphthalen-2-yloxy)-1-[(1,1'-biphenyl-4-yl)]ethan-1-one 在 盐酸羟胺 作用下， 以 乙醇 为溶剂， 反应 4.0h， 以64%的产率得到(Z)-1-(biphenyl-4-yl)-2-(naphthalen-2-yloxy)ethanone oxime
  参考文献：
  名称：

  Discovery of oxime-bearing naphthalene derivatives as a novel structural type of Nrf2 activators

  摘要：

  Recent studies have demonstrated that oxidative stress insult is one of major causes of tumor formation. Therefore, identify the effective anti-oxidative agents as a preventive approach to stop cancer progression has widely explored. Although, many potent anti-oxidative ingredients in the natural products have been identified but the amount from the nature source hindrances the clinical application. Compound which can activate Nrf2 signaling pathway result unregulated the cellular antioxidant-responses has been demonstrated as an effective chemopreventive approach for cancer treatment. In the present study, certain oxime-bearing naphthalene derivatives were synthesized and evaluated for their Nrf2 activation and anti-proliferative activities. Results indicated (E)-1-(naphthalen-2-yloxy) propan-2-one oxime (11) which increased 2.04-fold Nrf2/ARE-driven luciferase activity was more active than its 1-substituted isomer 10 (1.17-fold) and t-BHQ (1.77-fold), the known Nrf2 activator. The activities were further increased by the replacement of the peripheral methyl group with the phenyl ring in which (Z)-2-(naphthalen-2-yloxy)-1-phenylethanone oxime (13a) exhibited 3.49-fold potency of the positive control. It is worth to mention that compounds 11, 13a, and 13b which showed significant Nrf2 activation are non-cytotoxic to the tested cells with IC50 > 50 mu M. This observation strongly suggested that these compounds can be used for chemoprevention. Mechanism studies indicated that these compounds were capable of inducing the phosphorylation of Nrf2 protein at serine 40 which led to the activation of the Nrf2 transcriptional activity. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.03.046
• 作为产物：
  描述：

  2-溴-4-苯基乙酰苯 、 2-萘酚 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.5h， 以68%的产率得到2-(naphthalen-2-yloxy)-1-[(1,1'-biphenyl-4-yl)]ethan-1-one
  参考文献：
  名称：

  一系列针对癌细胞的γ-取代γ-芳氧基甲基-α-亚甲基-γ-丁内酯的合成和细胞毒性评估。

  摘要：

  目的本研究的主要目的是探讨γ-取代的γ-芳氧基甲基-α-亚甲基-γ-丁内酯对癌细胞的细胞毒性结构-活性关系。方法目标化合物的合成过程分为两步，首先是芳基-OH，后者是用溴甲基酮处理，然后进行Reformatsky型缩合反应。结果在体外针对来自9种癌细胞的60种人类癌细胞系评估了7种类型的α-亚甲基-γ-丁内酯。log GI50的平均值表明，对于芳基部分，这些α-亚甲基-γ-丁内酯的效能降序为quinolin-2（1H）-one（或2-hydroxyquinoline，21，-5.89）> quinoline （19，-5.79）> 2-甲基喹啉（20，-5.69）> 8-羟基喹啉（17，-5.64）> 2-萘（16，-5.59）>苯（15，-4.90）。log TGI和log LC50均获得相同的顺序。然而，对于γ-取代基，效力是联苯（16f-21f）>苯基和4-取代的苯基（16b-e-2

  DOI：

  10.1023/a:1007534416561

文献信息

• ——
  作者：Cheng-Chyi Tzeng、Kuan-Han Lee、Tai-Chi Wang、Chein-Hwa Han、Yeh-Long Chen

  DOI：10.1023/a:1007534416561

  日期：——

  Seven types of alpha-methylene-gamma-butyrolactones were evaluated in vitro against 60 human cancer cell lines derived from nine cancer cell types. The average values of log GI50 indicated that for the aryl portion, potencies of these alpha-methylene-gamma-butyrolactones are in a decreasing order of quinolin-2(1H)-one (or 2-hydroxyquinoline, 21, -5.89) > quinoline (19, -5.79) > 2-methylquinoline (20, -5

  目的本研究的主要目的是探讨γ-取代的γ-芳氧基甲基-α-亚甲基-γ-丁内酯对癌细胞的细胞毒性结构-活性关系。方法目标化合物的合成过程分为两步，首先是芳基-OH，后者是用溴甲基酮处理，然后进行Reformatsky型缩合反应。结果在体外针对来自9种癌细胞的60种人类癌细胞系评估了7种类型的α-亚甲基-γ-丁内酯。log GI50的平均值表明，对于芳基部分，这些α-亚甲基-γ-丁内酯的效能降序为quinolin-2（1H）-one（或2-hydroxyquinoline，21，-5.89）> quinoline （19，-5.79）> 2-甲基喹啉（20，-5.69）> 8-羟基喹啉（17，-5.64）> 2-萘（16，-5.59）>苯（15，-4.90）。log TGI和log LC50均获得相同的顺序。然而，对于γ-取代基，效力是联苯（16f-21f）>苯基和4-取代的苯基（16b-e-2
• Discovery of oxime-bearing naphthalene derivatives as a novel structural type of Nrf2 activators
  作者：Ken-Ming Chang、Fong-Pin Liang、I-Li Chen、Shyh-Chyun Yang、Shin-Hun Juang、Tai-Chi Wang、Yeh-Long Chen、Cherng-Chyi Tzeng

  DOI：10.1016/j.bmc.2015.03.046

  日期：2015.7

  Recent studies have demonstrated that oxidative stress insult is one of major causes of tumor formation. Therefore, identify the effective anti-oxidative agents as a preventive approach to stop cancer progression has widely explored. Although, many potent anti-oxidative ingredients in the natural products have been identified but the amount from the nature source hindrances the clinical application. Compound which can activate Nrf2 signaling pathway result unregulated the cellular antioxidant-responses has been demonstrated as an effective chemopreventive approach for cancer treatment. In the present study, certain oxime-bearing naphthalene derivatives were synthesized and evaluated for their Nrf2 activation and anti-proliferative activities. Results indicated (E)-1-(naphthalen-2-yloxy) propan-2-one oxime (11) which increased 2.04-fold Nrf2/ARE-driven luciferase activity was more active than its 1-substituted isomer 10 (1.17-fold) and t-BHQ (1.77-fold), the known Nrf2 activator. The activities were further increased by the replacement of the peripheral methyl group with the phenyl ring in which (Z)-2-(naphthalen-2-yloxy)-1-phenylethanone oxime (13a) exhibited 3.49-fold potency of the positive control. It is worth to mention that compounds 11, 13a, and 13b which showed significant Nrf2 activation are non-cytotoxic to the tested cells with IC50 > 50 mu M. This observation strongly suggested that these compounds can be used for chemoprevention. Mechanism studies indicated that these compounds were capable of inducing the phosphorylation of Nrf2 protein at serine 40 which led to the activation of the Nrf2 transcriptional activity. (C) 2015 Elsevier Ltd. All rights reserved.